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Lancet (London, England) Sep 2023Intravenous thrombolysis is recommended before endovascular treatment, but its value has been questioned in patients who are admitted directly to centres capable of... (Meta-Analysis)
Meta-Analysis
Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials.
BACKGROUND
Intravenous thrombolysis is recommended before endovascular treatment, but its value has been questioned in patients who are admitted directly to centres capable of endovascular treatment. Existing randomised controlled trials have indicated non-inferiority of endovascular treatment alone or have been statistically inconclusive. We formed the Improving Reperfusion Strategies in Acute Ischaemic Stroke collaboration to assess non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment.
METHODS
We conducted a systematic review and individual participant data meta-analysis to establish non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. We searched PubMed and MEDLINE with the terms "stroke", "endovascular treatment", "intravenous thrombolysis", and synonyms for articles published from database inception to March 9, 2023. We included randomised controlled trials on the topic of interest, without language restrictions. Authors of the identified trials agreed to take part, and individual participant data were provided by the principal investigators of the respective trials and collated centrally by the collaborators. Our primary outcome was the 90-day modified Rankin Scale (mRS) score. Non-inferiority of endovascular treatment alone was assessed using a lower boundary of 0·82 for the 95% CI around the adjusted common odds ratio (acOR) for shift towards improved outcome (analogous to 5% absolute difference in functional independence) with ordinal regression. We used mixed-effects models for all analyses. This study is registered with PROSPERO, CRD42023411986.
FINDINGS
We identified 1081 studies, and six studies (n=2313; 1153 participants randomly assigned to receive endovascular treatment alone and 1160 randomly assigned to receive intravenous thrombolysis and endovascular treatment) were eligible for analysis. The risk of bias of the included studies was low to moderate. Variability between studies was small, and mainly related to the choice and dose of the thrombolytic drug and country of execution. The median mRS score at 90 days was 3 (IQR 1-5) for participants who received endovascular treatment alone and 2 (1-4) for participants who received intravenous thrombolysis plus endovascular treatment (acOR 0·89, 95% CI 0·76-1·04). Any intracranial haemorrhage (0·82, 0·68-0·99) occurred less frequently with endovascular treatment alone than with intravenous thrombolysis plus endovascular treatment. Symptomatic intracranial haemorrhage and mortality rates did not differ significantly.
INTERPRETATION
We did not establish non-inferiority of endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment in patients presenting directly at endovascular treatment centres. Further research could focus on cost-effectiveness analysis and on individualised decisions when patient characteristics, medication shortages, or delays are expected to offset a potential benefit of administering intravenous thrombolysis before endovascular treatment.
FUNDING
Stryker and Amsterdam University Medical Centers, University of Amsterdam.
Topics: Humans; Stroke; Brain Ischemia; Intracranial Hemorrhages; Ischemic Stroke; Thrombolytic Therapy; Randomized Controlled Trials as Topic
PubMed: 37640037
DOI: 10.1016/S0140-6736(23)01142-X -
European Journal of Pharmacology Nov 2023Intestinal ischemia/reperfusion injury (IRI) is a multifactorial, complex pathophysiological process in clinical settings. In recent years, intestinal IRI has received... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intestinal ischemia/reperfusion injury (IRI) is a multifactorial, complex pathophysiological process in clinical settings. In recent years, intestinal IRI has received increasing attention due to increased morbidity and mortality. To date, there are no effective treatments. Dexmedetomidine (DEX), a highly selective α-adrenergic receptor agonist, has been demonstrated to be effective against intestinal IRI. In this systematic review and meta-analysis, we evaluated the efficacy and potential mechanisms of DEX as a treatment for intestinal IRI in animal models.
METHODS
Five databases (PubMed, Embase, Web of Science, Cochrane Library, and Scopus) were searched until March 15, 2023. Using the SYRCLE risk bias tool, we assessed methodological quality. Statistical analysis was conducted using STATA 12 and R 4.2.2. We analyzed the related outcomes (mucosa damage-related indicators; inflammation-relevant markers, oxidative stress markers) relied on the fixed or random-effects models.
RESULTS
There were 15 articles including 18 studies included, and 309 animals were involved in the studies. Compared to the model groups, DEX improved intestinal IRI. DEX decreased Chiu's score and serum diamine oxidase (DAO) level. DEX reduced the level of inflammation-relevant markers (interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α). DEX also improved oxidative stress (decreased malondialdehyde (MDA), increased superoxide dismutase (SOD)).
CONCLUSIONS
DEX's effectiveness in ameliorating intestinal IRI has been demonstrated in animal models. Antioxidation, anti-inflammation, anti-apoptotic, anti-pyroptosis, anti-ferroptosis, enhancing mitophagy, reshaping the gut microbiota, and gut barrier protection are possible mechanisms. However, in light of the heterogeneity and methodological quality of these studies, further well-designed preclinical studies are warranted before clinical implication.
Topics: Rats; Animals; Dexmedetomidine; Rats, Sprague-Dawley; Adrenergic alpha-2 Receptor Agonists; Reperfusion Injury; Inflammation; Ischemia
PubMed: 37778612
DOI: 10.1016/j.ejphar.2023.176090 -
The Journal of Surgical Research Dec 2023Heart transplantation is the treatment of choice for end-stage heart failure. There is a mismatch between the number of donor hearts available and the number of patients... (Review)
Review
INTRODUCTION
Heart transplantation is the treatment of choice for end-stage heart failure. There is a mismatch between the number of donor hearts available and the number of patients awaiting transplantation. Expanding the donor pool is critically important. The use of hearts donated following circulatory death is one approach to increasing the number of available donor hearts.
MATERIALS AND METHODS
A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines utilizing Pubmed/MEDLINE and Embase. Articles including adult human studies and preclinical animal studies of heart transplantation following donation after circulatory death were included. Studies of pediatric populations or including organs other than heart were excluded.
RESULTS
Clinical experience and preclinical studies are reviewed. Clinical experience with direct procurement, normothermic regional perfusion, and machine perfusion are included. Preclinical studies addressing organ function assessment and enhancement of performance of marginal organs through preischemic, procurement, preservation, and reperfusion maneuvers are included. Articles addressing the ethical considerations of thoracic transplantation following circulatory death are also reviewed.
CONCLUSIONS
Heart transplantation utilizing organs procured following circulatory death is a promising method to increase the donor pool and offer life-saving transplantation to patients on the waitlist living with end-stage heart failure. There is robust ongoing preclinical and clinical research to optimize this technique and improve organ yield. There are also ongoing ethical considerations that must be addressed by consensus before wide adoption of this approach.
PubMed: 37657140
DOI: 10.1016/j.jss.2023.07.050 -
The Cochrane Database of Systematic... Sep 2023Liver transplantation is the only chance of cure for people with end-stage liver disease and some people with advanced liver cancers or acute liver failure. The... (Review)
Review
BACKGROUND
Liver transplantation is the only chance of cure for people with end-stage liver disease and some people with advanced liver cancers or acute liver failure. The increasing prevalence of these conditions drives demand and necessitates the increasing use of donated livers which have traditionally been considered suboptimal. Several novel machine perfusion preservation technologies have been developed, which attempt to ameliorate some of the deleterious effects of ischaemia reperfusion injury. Machine perfusion technology aims to improve organ quality, thereby improving outcomes in recipients of suboptimal livers when compared to traditional static cold storage (SCS; ice box).
OBJECTIVES
To evaluate the effects of different methods of machine perfusion (including hypothermic oxygenated machine perfusion (HOPE), normothermic machine perfusion (NMP), controlled oxygenated rewarming, and normothermic regional perfusion) versus each other or versus static cold storage (SCS) in people undergoing liver transplantation.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 10 January 2023.
SELECTION CRITERIA
We included randomised clinical trials which compared different methods of machine perfusion, either with each other or with SCS. Studies comparing HOPE via both hepatic artery and portal vein, or via portal vein only, were grouped. The protocol detailed that we also planned to include quasi-randomised studies to assess treatment harms.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. overall participant survival, 2. quality of life, and 3. serious adverse events. Secondary outcomes were 4. graft survival, 5. ischaemic biliary complications, 6. primary non-function of the graft, 7. early allograft function, 8. non-serious adverse events, 9. transplant utilisation, and 10. transaminase release during the first week post-transplant. We assessed bias using Cochrane's RoB 2 tool and used GRADE to assess certainty of evidence.
MAIN RESULTS
We included seven randomised trials (1024 transplant recipients from 1301 randomised/included livers). All trials were parallel two-group trials; four compared HOPE versus SCS, and three compared NMP versus SCS. No trials used normothermic regional perfusion. When compared with SCS, it was uncertain whether overall participant survival was improved with either HOPE (hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.42 to 1.98; P = 0.81, I = 0%; 4 trials, 482 recipients; low-certainty evidence due to imprecision because of low number of events) or NMP (HR 1.08, 95% CI 0.31 to 3.80; P = 0.90; 1 trial, 222 recipients; very low-certainty evidence due to imprecision and risk of bias). No trials reported quality of life. When compared with SCS alone, HOPE was associated with improvement in the following clinically relevant outcomes: graft survival (HR 0.45, 95% CI 0.23 to 0.87; P = 0.02, I = 0%; 4 trials, 482 recipients; high-certainty evidence), serious adverse events in extended criteria DBD liver transplants (OR 0.45, 95% CI 0.22 to 0.91; P = 0.03, I = 0%; 2 trials, 156 participants; moderate-certainty evidence) and clinically significant ischaemic cholangiopathy in recipients of DCD livers (OR 0.31, 95% CI 0.11 to 0.92; P = 0.03; 1 trial, 156 recipients; high-certainty evidence). In contrast, NMP was not associated with improvement in any of these clinically relevant outcomes. NMP was associated with improved utilisation compared with SCS (one trial found a 50% lower rate of organ discard; P = 0.008), but the reasons underlying this effect are unknown. We identified 11 ongoing studies investigating machine perfusion technologies.
AUTHORS' CONCLUSIONS
In situations where the decision has been made to transplant a liver donated after circulatory death or donated following brain death, end-ischaemic HOPE will provide superior clinically relevant outcomes compared with SCS alone. Specifically, graft survival is improved (high-certainty evidence), serious adverse events are reduced (moderate-certainty evidence), and in donors after circulatory death, clinically relevant ischaemic biliary complications are reduced (high-certainty evidence). There is no good evidence that NMP has the same benefits over SCS in terms of these clinically relevant outcomes. NMP does appear to improve utilisation of grafts that would otherwise be discarded with SCS; however, the reasons for this, and whether this effect is specific to NMP, is not clear. Further studies into NMP viability criteria and utilisation, as well as head-to-head trials with other perfusion technologies are needed. In the setting of donation following circulatory death transplantation, further trials are needed to assess the effect of these ex situ machine perfusion methods against, or in combination with, normothermic regional perfusion.
Topics: Humans; Liver Transplantation; Quality of Life; Perfusion; End Stage Liver Disease
PubMed: 37698189
DOI: 10.1002/14651858.CD014685.pub2 -
Neurology Apr 2024Remote ischemic conditioning (RIC) is a low-cost, accessible, and noninvasive neuroprotective treatment strategy, but its efficacy and safety in acute ischemic stroke... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Remote ischemic conditioning (RIC) is a low-cost, accessible, and noninvasive neuroprotective treatment strategy, but its efficacy and safety in acute ischemic stroke are controversial. With the publication of several randomized controlled trials (RCTs) and the recent results of the RESIST trial, it may be possible to identify the patient population that may (or may not) benefit from RIC. This systematic review and meta-analysis aims to evaluate the effectiveness and safety of RIC in patients with ischemic stroke receiving different treatments by pooling data of all randomized controlled studies to date.
METHODS
We searched the PubMed, Embase, Cochrane, Elsevier, and Web of Science databases to obtain articles in all languages from inception until May 25, 2023. The primary outcome was the modified Rankin Scale (mRS) score at the specified endpoint time in the trial. The secondary outcomes were change in NIH Stroke Scale (NIHSS) and recurrence of stroke events. The safety outcomes were cardiovascular events, cerebral hemorrhage, and mortality. The quality of articles was evaluated through the Cochrane risk assessment tool. This study was registered in PROSPERO (CRD42023430073).
RESULTS
There were 7,657 patients from 22 RCTs included. Compared with the control group, patients who received RIC did not have improved mRS functional outcomes, regardless of whether they received medical management, reperfusion therapy with intravenous thrombolysis (IVT), or mechanical thrombectomy (MT). In the medical management group, patients who received RIC had decreased incidence of stroke recurrence (risk ratio 0.63, 95% CI 0.43-0.92, = 0.02) and lower follow-up NIHSS score by 1.72 points compared with the control group ( < 0.00001). There was no increased risk of adverse events including death or cerebral hemorrhage in the IVT or medical management group.
DISCUSSION
In patients with ischemic stroke who are not eligible for reperfusion therapy, RIC did not affect mRS functional outcomes but significantly improved the NIHSS score at the follow-up endpoint and reduced stroke recurrence, without increasing the risk of cerebral hemorrhage or death. In patients who received IVT or MT, the benefit of RIC was not observed.
Topics: Humans; Fibrinolytic Agents; Brain Ischemia; Thrombolytic Therapy; Stroke; Cerebral Hemorrhage; Ischemic Stroke; Reperfusion; Treatment Outcome; Thrombectomy
PubMed: 38457772
DOI: 10.1212/WNL.0000000000207983 -
Frontiers in Pharmacology 2024Cerebral ischemia-reperfusion (I/R) injury is the predominant causes for the poor prognosis of ischemic stroke patients after reperfusion therapy. Currently, potent... (Review)
Review
Cerebral ischemia-reperfusion (I/R) injury is the predominant causes for the poor prognosis of ischemic stroke patients after reperfusion therapy. Currently, potent therapeutic interventions for cerebral I/R injury are still very limited. Melatonin, an endogenous hormone, was found to be valid in preventing I/R injury in a variety of organs. However, a systematic review covering all neuroprotective effects of melatonin in cerebral I/R injury has not been reported yet. Thus, we perform a comprehensive overview of the influence of melatonin on cerebral I/R injury by collecting all available literature exploring the latent effect of melatonin on cerebral I/R injury as well as ischemic stroke. In this systematic review, we outline the extensive scientific studies and summarize the beneficial functions of melatonin, including reducing infarct volume, decreasing brain edema, improving neurological functions and attenuating blood-brain barrier breakdown, as well as its key protective mechanisms on almost every aspect of cerebral I/R injury, including inhibiting oxidative stress, neuroinflammation, apoptosis, excessive autophagy, glutamate excitotoxicity and mitochondrial dysfunction. Subsequently, we also review the predictive and therapeutic implications of melatonin on ischemic stroke reported in clinical studies. We hope that our systematic review can provide the most comprehensive introduction of current advancements on melatonin in cerebral I/R injury and new insights into personalized diagnosis and treatment of ischemic stroke.
PubMed: 38375039
DOI: 10.3389/fphar.2024.1356112 -
Frontiers in Neurology 2023The impact of COVID-19 on clinical outcomes in acute ischemic stroke patients receiving reperfusion therapy remains unclear. We therefore aimed to synthesize the... (Review)
Review
BACKGROUND
The impact of COVID-19 on clinical outcomes in acute ischemic stroke patients receiving reperfusion therapy remains unclear. We therefore aimed to synthesize the available evidence to investigate the safety and short-term efficacy of reperfusion therapy in this patient population.
METHODS
We searched the electronic databases MEDLINE, Embase and Cochrane Library Reviews for randomized controlled trials and observational studies that investigated the use of intravenous thrombolysis, endovascular therapy, or a combination of both in acute ischemic stroke patients with laboratory-confirmed COVID-19, compared to controls. Our primary safety outcomes included any intracerebral hemorrhage (ICH), symptomatic ICH and all-cause in-hospital mortality. Short-term favorable functional outcomes were assessed at discharge and at 3 months. We calculated pooled risk ratios (RR) and 95% confidence intervals (CI) using DerSimonian and Laird random-effects model. Heterogeneity was evaluated using Cochran's Q test and statistics.
RESULTS
We included 11 studies with a total of 477 COVID-19 positive and 8,092 COVID-19 negative ischemic stroke patients who underwent reperfusion therapy. COVID-19 positive patients exhibited a significantly higher risk of experiencing any ICH (RR 1.54, 95% CI 1.16-2.05, < 0.001), while the nominally increased risk of symptomatic ICH in these patients did not reach statistical significance (RR 2.04, 95% CI 0.97-4.31; = 0.06). COVID-19 positive stroke patients also had a significantly higher in-hospital mortality compared to COVID-19 negative stroke patients (RR 2.78, 95% CI 2.15-3.59, < 0.001). Moreover, COVID-19 positive stroke patients were less likely to achieve a favorable functional outcome at discharge (RR 0.66, 95% CI 0.51-0.86, < 0.001) compared to COVID-19 negative patients, but this difference was not observed at 3-month follow-up (RR 0.64, 95% CI 0.14-2.91, = 0.56).
CONCLUSION
COVID-19 appears to have an adverse impact on acute ischemic stroke patients who undergo reperfusion therapy, leading to an elevated risk of any ICH, higher mortality and lower likelihood of favorable functional outcome.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42022309785.
PubMed: 37681003
DOI: 10.3389/fneur.2023.1239953 -
International Journal of Stroke :... Dec 2023Endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) have an unclear benefit in those with pre-stroke dementia or cognitive impairment, as these patients... (Review)
Review
BACKGROUND
Endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) have an unclear benefit in those with pre-stroke dementia or cognitive impairment, as these patients were often excluded from landmark stroke trials. We performed a systematic review and meta-analysis to assess the outcomes of IVT and EVT in these populations.
AIMS
Our systematic review, conforming to the Meta-Analysis of Observational Studies in Epidemiology guidelines, investigated studies on acute ischemic stroke patients with pre-stroke dementia or cognitive impairment treated with IVT or EVT. Primary outcome was favorable 90-day outcome (mRS 0-2). Secondary outcomes included 90-day mortality, symptomatic intracranial hemorrhage (SICH), and radiographic intracranial hemorrhage (ICH).
SUMMARY OF REVIEW
Nine articles were identified, with five observational studies of IVT use in patients with (n = 1078) and without dementia (n = 2805) being selected for the meta-analysis. There were no significant differences in favorable outcome (adjusted OR: 0.61, 95% CI 0.24-1.59), mortality (unadjusted OR: 1.19, 95% CI 0.86-1.64), ICH (unadjusted OR: 1.32, 95% CI 0.79-2.19), and symptomatic ICH (unadjusted OR: 0.94, 95% CI 0.70-1.25) for patients undergoing IVT with pre-stroke dementia versus those without. One EVT study (n = 615 with dementia vs n = 9600 without) found no significant differences in outcomes apart from an increased odds of ICH for those with pre-existing dementia (adjusted OR: 1.57, 95% CI 1.03-2.40). A pooled analysis of three IVT studies showed no significant association of cognitive impairment (n = 93 vs n = 211 without) with all assessed outcomes, whereas a study of EVT found that pre-stroke cognitive impairment was associated with poor 90-day outcomes (mRS 3-6).
CONCLUSION
These results suggest no substantial safety issues in the use of IVT or EVT for patients with pre-existing dementia or cognitive impairment compared to those without. However, the efficacy of these therapies in this demographic remains uncertain. Further rigorous studies that include a more nuanced outcome measurement approach are warranted.
REGISTRATION
URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021240499.
PubMed: 38044328
DOI: 10.1177/17474930231220186 -
Clinical Neurology and Neurosurgery Sep 2023About 30 % of stroke patients have experienced unsuccessful reperfusion following endovascular therapy. Mechanical thrombectomy instruments may contribute to this by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
About 30 % of stroke patients have experienced unsuccessful reperfusion following endovascular therapy. Mechanical thrombectomy instruments may contribute to this by stimulating platelet aggregation. Tirofiban is a selective and rapidly activated antagonist of the platelets nonpeptide glycoprotein IIb/IIIa receptors that can reversibly suppress platelet aggregation. But, data from the medical literature are conflicting regarding its safety and efficacy for stroke patients. Hence, this study was designed to assess the safety and efficacy of tirofiban in stroke patients.
METHODS
Five major databases (PubMed, Scopus, Web of Science, Embase, and Cochrane library) were searched till December 2022. The Cochrane tool was used for risk of bias assessment, and the RevMan 5.4 was utilized for data analysis.
RESULTS
Seven RCTs with 2088 stroke patients were included. Tirofiban significantly increased the number of patients with mRS 0 score after 90 days than control; RR= 1.39, 95 %CI [1.15, 1.69]; p = 0.0006. Additionally, it reduced the NIHSS score after seven days; MD= -0.60, 95 %CI [-1.14, -0.06]; p = 0.03. However, tirofiban increased the incidence of intracranial haemorrhage (ICH); RR= 1.22, 95 %CI [1.03, 1.44]; p = 0.02. Other assessed outcomes showed insignificant results.
CONCLUSIONS
Tirofiban was associated with a higher mRS 0 score after three months and a lower NIHSS score after seven days. However, it is associated with higher ICH. Multicentric trials are required to provide more convincing proof of its utility.
Topics: Humans; Tirofiban; Platelet Aggregation Inhibitors; Brain Ischemia; Treatment Outcome; Randomized Controlled Trials as Topic; Stroke; Intracranial Hemorrhages
PubMed: 37423089
DOI: 10.1016/j.clineuro.2023.107867 -
Journal of Pharmaceutical Policy and... Aug 2023Acute coronary syndrome (ACS) is the principal cause of death in developing countries including Ethiopia. No study reports the overall patterns of risk factors and... (Review)
Review
BACKGROUND
Acute coronary syndrome (ACS) is the principal cause of death in developing countries including Ethiopia. No study reports the overall patterns of risk factors and burden of in-hospital mortality in Ethiopia. This study, therefore, aimed to assess the magnitude of risk factors, management, and in-hospital mortality of ACS in Ethiopia.
METHODS
Electronic searching of articles was conducted using PubMed, Science Direct, EMBASE, Scopus, Hinari, and Google Scholar to access articles conducted in Ethiopia. The Preferred Reporting Items for Systematic Reviews checklist was used for identification, eligibility screening, and selection of articles. Data were extracted with an abstraction form prepared with Microsoft Excel and exported to STATA for analysis. Funnel plot, Begg's test, and Egger's test were used to determine publication bias. Heterogeneity between the studies was checked by I statistic. The pooled prevalence of risk factors and in-hospital mortality of ACS were estimated using a random-effects meta-analysis model.
RESULTS
Most (59.367%) of the patients had ST-segment elevation myocardial infarction (STEMI). Hypertension (54.814%) was the leading risk factor for ACS followed by diabetes mellitus (38.549%). Aspirin (56.903%) and clopidogrel (55.266%) were most frequently used in patients with STEMI ACS, respectively. The pooled proportion of in-hospital mortality of ACS was 14.82% which was higher in patients with STEMI (16.116%).
CONCLUSION
The rate of in-hospital mortality is still high which was higher in patients with STEMI. Initiation of treatment must consider the heterogeneity of each patient's risk factor and reperfusion therapy should be implemented in our setting.
PubMed: 37550741
DOI: 10.1186/s40545-023-00603-7